Use of an histone deacetylase inhibitor for the treatment of diseases associated with an hpv infection

Inactive Publication Date: 2004-07-08
DEUTES KREBSFORSCHUNGSZENT STIFTUNG DES OFFENTLICHEN RECHTS
View PDF3 Cites 9 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

0006] Described is the use of histone deacetylase inhibitors for the treatment of a disease, preferably cervical cancer,

Problems solved by technology

Unfortunately, the different strategies employed so far for therapy gave only discouraging results.
However, at present it is unclear whether these strategies will ever work, since, e.g., as regards antisense-based approaches it is entirely open as to whether in vivo any effect by onc

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Use of an histone deacetylase inhibitor for the treatment of diseases associated with an hpv infection
  • Use of an histone deacetylase inhibitor for the treatment of diseases associated with an hpv infection
  • Use of an histone deacetylase inhibitor for the treatment of diseases associated with an hpv infection

Examples

Experimental program
Comparison scheme
Effect test

example 1

A. Example 1

General Methods

[0053] 1. Cell Lines

[0054] HPV18-positive cervical Carcinoma cells (HeLa) were maintained in Dulbecco's modified Eagle's medium (DMEM), supplemented with 10% fetal calf serum (Gibco BRL, Rockville, USA), 1% penicillin and streptomycin (Sigma, Deisenhofen, Deutschland). Primary human keratinocytes, immortalized by E6-, E7- and E6 / E7-open reading frames carrying amphotroptic retroviruses were cultivated in "Keratinocyte Medium Kit" (Sigma). Human foreskin keratinocytes transformed with HPV-16 E6 / E7 either under the control of a human .beta.-actin promoter (,,1321") or under the control of the authentic upstream regulatory region HPV (,,1637") were a kind gift of Dr. R. Schlegel (Georgetown University, Washington, USA) (Munger et al., J. Virol. 63 (1989), 4414-4423; Villa & Schlegel, Virology 181 (1991), 374-377). Cells were grown in 3 parts of keratinocyte-serum free medium (K-SFM, GIBCO, BRL) and 1 part of DMEM containing 10% fetal calf serum (GIBCO, BRL) a...

example 2

B. Example 2

Histone Deacetylase (HDAC) Inhibitors Induce G1 / S Phase Arrest in HIPV18-Positive Cervical Carcinoma Cells Despite Ongoing E6 / E7 Synthesis

[0071] Modulation of histone acetylation is an integral part of a regulatory mechanism, which is involved in the nucleosomal organization of the bulk cellular DNA. Posttranslational neutralisation of the positive charge of lysine residues within the N-terminal domain of core histones relieves histone-DNA interactions, which in turn facilitates the accessibility of transcription factors with their cognate regulatory elements at the DNA level. Alterations of the chromatin architecture is mediated by an interplay between histone acetylases (HAT) and deacetylases (HDAC) counteracting each other in either activating or repressing gene expression. During the last years, a substantial number of HATs have been characterized in yeast and Tetrahymena. In higher eukaryotes, particular adaptor molecules such as p300 / CBP or p / CAF (termed as p300 / CP...

example 3

C. Example 3

HDAC Inhibitors Modulate Cyclins but not Cdk Expression

[0075] Because the precise mechanism underlying the growth inhibitory effect on cervical carcinoma cells has not yet been established, the steady-state levels of regulatory proteins involved in cell cycle control were examined. As shown in FIG. 2, sodium butyrate selectively downregulates cyclin D1 and cyclin A, while the amount of cyclin E was strongly increased (FIG. 2A). Incubation of the same filter with a monoclonal actin antibody confirmed equal loading and protein transfer. Quantitative differences of cyclin expression after sodium butyrate application were presumably not due to altered degradation rates, since there was a good accordance between the levels of protein and the corresponding mRNAs (FIG. 2C). Control hybridization of the identical blot with glyceraldehyde-3-phosphate dehydrogenase (GAPDH) again corroborated the selectivity of this effect. In contrast, neither the cyclin-dependent kinase 2 (cdk2) ...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

Abstract

Described is the use of histone deacetylase inhibitors for the treatment of a disease, preferably cervical cancer, associated with an HPV infection. Particularly useful inhibitors are sodium butyrate, phenylbutyrate and trichostatin A.

Description

[0001] This application is a national stage filing of international application PCT / EP02 / 04004, filed Apr. 10, 2002, which claims priority to European application No. EP01108923.2, filed Apr. 10, 2001, each incorporated by reference in their entirety.I. FIELD OF THE INVENTION[0002] The present invention relates to the use of histone deacetylase inhibitors for the treatment of a disease, preferably cervical cancer, associated with an HPV infection. Particularly useful inhibitors are sodium butyrate, phenylbutyrate and trichostatin A.II. BACKGROUND OF THE INVENTION[0003] Carcinoma of the uterine cervix (cervical cancer, CC) is the second most common cancer in women worldwide and the first in developing countries. CC develops through premalignant intermediate stages of increasing severity known as cervical intraepithelial neoplasm (CIN) grades 1-3, the latter leading to the development of invasive cancer in about 50% of cases over a period of 1-2 decades. More than 11% of the global ca...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
IPC IPC(8): A61K31/00A61K31/165A61K31/19A61K31/192A61P35/00
CPCA61K31/00A61K31/192A61K31/19A61K31/165A61P35/00
Inventor FINZER, PATRICKROSL, FRANKZUR HAUSEN, HARALD
Owner DEUTES KREBSFORSCHUNGSZENT STIFTUNG DES OFFENTLICHEN RECHTS
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap